CLOCK and gastric cancer: Specifically, in human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer, the circadian oscillation of glycolysis controlled by hexokinase 2 (HK2) and PER1 contributes to trastuzumab resistance, which is an inevitable major problem in chemotherapy targeting HER2 using that drug, whereas Metformin-based chronotherapy disrupts the BMAL1-CLOCK-PER1-HK2 axis, affecting glycolysis oscillation to overcome trastuzumab resistance [315].